Abstract

Polymorphonuclear neutrophils (PMN) are potent inflammatory effector cells essential to host defense, but at the same time they may cause significant tissue damage. Thus, timely induction of neutrophil apoptosis is crucial to avoid tissue damage and induce resolution of inflammation. NK cells have been reported to influence innate and adaptive immune responses by multiple mechanisms including cytotoxicity against other immune cells. In this study, we analyzed the effect of the interaction between NK cells and neutrophils. Coculture experiments revealed that human NK cells could trigger caspase-dependent neutrophil apoptosis in vitro. This event was dependent on cell–cell contact, and experiments using blocking Abs indicated that the effect was mediated by the activating NK cell receptor NKp46 and the Fas pathway. CD56-depleted lymphocytes had minimal effects on neutrophil survival, suggesting that the ability to induce neutrophil apoptosis is specific to NK cells. Our findings provide evidence that NK cells may accelerate neutrophil apoptosis, and that this interaction may be involved in the resolution of acute inflammation.

Footnotes

This work was supported by grants awarded by Associazione Italiana Ricerca sul Cancro (Investigator grant [IG] project 10643, to A.M.; IG project 4725, to L.M.; and Special Project 5x1000 9962, to A.M. and L.M.), University of Genoa (Progetto Ricerca Ateneo 2010, to E.M.), Swedish Medical Research Council, King Gustaf V’s Memorial Foundation, Gunvor and Ivan Svensson’s Foundation, and the Swedish State under the LUA/ALF agreement; by the European Molecular Biology Organization (EMBO; EMBO long-term fellowship to F.B.T.); and by the European Commission (Marie Curie Intra-European Fellowship to F.B.T.).